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Effect of cefoxitin and clindamycin on selection of derepressed mutants in Enterobacter cloacae
D Saverino1, F Milintenda-Floriani, A A Medeiros
1Department of Experimental Medicine, Section of Human Anatomy, University of Genova, Italy.
Abstract:
The characteristics of an antibiotic that favor its ability to select for resistant bacteria are not completely understood. Otherwise, by the common use of broad-spectrum cephalosporins, resistant strains of several gram-negative species, especially Enterobacter cloacae, have been more frequently isolated. During our studies on beta-lactam resistance in E. cloacae, we observed that the addition of an inhibitor (clindamycin) to a potent inducer (cefoxitin) leads to an enhanced selection of resistant mutants. This could explain the emergence of beta-lactam resistant strains during antibiotic therapy.
Insights
Antibiotic combinations can unexpectedly promote the development of resistant bacteria. Specifically, using an inducer with an inhibitor, like cefoxitin and clindamycin, enhanced the selection of beta-lactam resistant Enterobacter cloacae.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Antibiotic resistance is a growing global health threat, particularly among gram-negative bacteria.
- The mechanisms by which antibiotics select for resistant strains are not fully elucidated.
- Increased isolation of resistant Enterobacter cloacae has been linked to broad-spectrum cephalosporin use.
Purpose of the Study:
- To investigate the factors influencing antibiotic selection of resistant bacterial mutants.
- To understand the impact of combined antibiotic administration on resistance development in Enterobacter cloacae.
Main Methods:
- Studied beta-lactam resistance in Enterobacter cloacae.
- Utilized cefoxitin (a potent inducer) and clindamycin (an inhibitor) in combination.
- Observed the selection of resistant mutants under these conditions.
Main Results:
- The combination of cefoxitin and clindamycin resulted in enhanced selection of resistant mutants.
- This synergistic effect was observed in Enterobacter cloacae.
- Suggests a mechanism for the emergence of antibiotic resistance during combination therapy.
Conclusions:
- Certain antibiotic combinations can accelerate the emergence of resistant bacterial strains.
- The co-administration of inducers and inhibitors may potentiate resistance selection.
- Findings provide insights into antibiotic resistance mechanisms during therapeutic interventions.
